Measurement of DNA damage with endonucleases, which recognize lesions such as pyrimidine diemrs or ionizing radiation base damage, has been used to study DNA repair in mammalian cells. The sensitivity of this approach has been increased 1 to 2 orders of magnitude by adapting it to the alkaline elution technique. In the case of ionizing radiation, enzyme preparations from M. luteus or E. Coli can now be used to detect base damage and its repair in human cells after biologically relevant doses. We have recently concluded dose response and repair kinetic studies in normal human fibroblasts after X-irradiation. We have initiated studies using X-ray sensitive strains, such as from patients with ataxia telangiectasia. In the case of UV-radiation, our approach has been used to show that a small fraction of pyrimidine dimers are exchanged into DNA synthesized after UV by a recombination process somewhat analogous to recombination repair in bacteria. Possible abnormalities in recombination repair will be studied in likely cnancer-prone diseases such as Bloom's syndrome and the variant form of xeroderma pigmentosum.